Notes on Nobel Laureate Dr. David Baltimore's Historic Trip to South Africa

Dr. David Baltimore, was the presenter of the Nelson Mandela Science Lecture at Wittsvaterstrand(WITS) University in Johannesburg, South Africa on October 5th. As the event organizer, I documented Dr. Baltimore's trip to South Africa and Rwanda.

Shortly after arriving in Johannesburg two weeks ago, Dr. Baltimore was preparing to give the event's keynote lecture, concerning the many approaches to curing the viruses that pose the greatest danger to humanity.

However, the crowd gathering to hear him in the auditorium was unaware that there were events beyond their control taking place outside on the university campus. Sparked by a rise in student fees, student demonstrators were taking over the campus.

When I informed Dr. Baltimore of the precarious situation developing outside he reacted coolly, saying he would continue the lecture despite the noisy distraction coming from the protesting students outside the auditorium.

On the way to Dr. Baltimore's lecture, he, myself and Dr. Wilmot James, head of the Africa Genome Education Institute, visited Nelson Mandela at his Foundation. Dr. James wrote the forward to one of Mandela's biographies. During the meeting, Dr. Baltimore told Mandela that he had just endorsed Hillary Clinton for President, due to his approval of her newly announced scientific agenda. Dr. Baltimore stated that he would do all in his power to aid research in the United States that will hopefully soon lead to a vaccine or cure for the HIV/AIDS virus.

We went on to WITS at noon for the lecture. As David Baltimore rose to speak there was a smoke and thunder of voices, rattling of the doors at the back of the Great Hall at WITS. Protestors threatened to disrupt the third annual Nelson Mandela Science Lecture.

Baltimore, the President Emeritus and Robert Andrews Millikan Professor of Biology at CalTech whose work on the identification of reverse transcriptase the mechanism by which retroviruses, like HIV, infect cells -- earned him the 1975 Nobel Prize in Physiology or Medicine at the age of 37.

Africa, with 10% of the world's population, has 60% of its infections. In 1994 South Africa, at the dawn of transition to majority rule, already had 850,000 people infected with HIV. In 2007, largely as a result of government negligence and the promotion of "alternative" remedies such as garlic and beetroot, there are 5.5 million South Africans who are HIV positive. Surprisingly this is the first time that Baltimore has been to Johannesburg and Rwanda.

The students outside the Great Hall, held back by campus security, weren't concerned about AIDS. They were protesting the university's decision to raise fees, expressing their displeasure by emptying garbage out of bins and interrupting lectures ­ nothing violent. It is said that approx 20% of students at WITS are HIV positive.

Inside the hall a student yelled to Baltimore, "You're my hero! You rock!" Baltimore laughed.

HIV was identified in 1981 and is now the most studied virus in science. It is also history's most destructive, estimated to have been responsible for the deaths of 25 million people. Three years ago the Gates Foundation offered grants for the study of audacious new approaches to combating HIV. Baltimore was one of the recipients for a gene therapy approach and he is now building the tools necessary for it to work.

In the speech, Baltimore said that if you are going to think about the most complicated issues in science, then you must be prepared to be wrong. That doesn't ameliorate the awful disappointment at the failure of the phase II Merck HIV vaccine trial. Merck's vaccine was hoped to stimulate an immune response in the body's T-cells, enabling them to recognize and destroy the HIV virus. The greatest difficulty facing vaccine researchers has been that none of their laboratory subjects (chimpanzees and/or mice) are affected by HIV in the precisely the same way as humans, making it nearly impossible to tell how a vaccine will work in a human population.

Baltimore said he had found a way around this impasse by using gene therapy to create a mouse, which has an immune system highly similar to humans. One-day-old mice are injected with human stem cells that then supplant the mice's own immune systems.

Gene therapy requires that new genes be incorporated into the human genome to express new proteins to combat HIV in novel ways. "Interestingly," says Baltimore, "the virus that is a natural for this role is HIV itself."

"Retroviruses operate by integrating themselves into their host's DNA" he explained in the lecture. "The enzyme responsible for kicking off the process that synthesises a DNA copy of the RNA virus is reverse transcriptase. Interfere with the operation of reverse transcriptase and HIV is unable to function. Many of the anti-viral therapies for HIV have taken this approach."

Baltimore himself is now building genes to target the enzyme the identification of which earned him his Nobel Prize.

A science student at WITS asked Baltimore, "How does one target the action of reverse transcriptase?"

The answer from Baltimore was: "Micro RNA is a very exciting new discovery of one approach. Micro RNA (miRNA) are tiny lengths of RNA, containing no genes, which regulate gene expression directly. The miRNA is complementary to messenger RNA (which carries the code for protein production) and acts to dampen gene expression. In other words, it is an off switch."

Other points of note from Baltimore's remarks were: 1. Novel miRNAs could be produced to interfere with HIV RNA synthesis to DNA. 500 miRNAs have been identified and there is an enormous amount of work still to perform. Baltimore has just been appointed to be head of a scientific panel advising a new business looking into this.

2. Another area is histone modification. Histones are proteins which act as spools around which DNA winds, and play a role in gene expression. They could be used to turn whole regions of genes on or off. However, gene approaches run risks of how patients respond.

3. Amgen, a company where Baltimore is a director, has a drug called Vectibix. It is used for the treatment of colorectal cancer and inhibits the epidermal growth factor receptor (EGFr). They have recently discovered that only 15% of patients respond to the therapy. It appears that the bulk of patients have EGFr genes with mutations downstream of the gene that are sufficient to prevent the efficacy of the drug.

4. It could be that a gene therapy approach to HIV runs into similar complications. This opens up the necessity for pharmacogenetics where remedies are targeted to specific expressions of particular ailments.

"It may be that I can't pull off the gene therapy approach," said Baltimore, at the end of the hour long lecture. "But I think we will. The Gates Foundation only wants to fund things that are a great challenge. If you spend a lifetime in research doing this you'll probably never get funded. But, occasionally, you've got to be willing to take a giant leap."

The applause was deafening at the conclusion of the talk. Baltimore was thanked profusely by the WITS University Chancellor and the director of the Department of Science. The students had stayed away from the lecture hall as HIV/AIDS was not their concern that day.

On his return to Pasadena from Africa earlier this week I called Baltimore for news of his visit to the President of Rwanda. He was elated by his trip to Africa and explained: "Rwanda is the leader in AIDS research. Rwanda is special. They are building a country on the back of genocide. They are committed to do the right thing. They have the best system in the world for monitoring AIDS treatment. Built and run by them with their own software."

Comments

[ohjaygee]

...sadly small mindedness, personal agendas and petty politics are hindering my country in following the lead of others - we're already in a genocide of our own making and a long way off from getting a true committment to recognising let alone doing the right thing....

[dgscol]

He is better at raising funds than finding solutions- which a big name may be able to do. At NIH he was involved in publishing many reports based on faked, reconstituted, and fudged data. Hopefully those days are in the past, for the sake of all those unfortunates in S Africa with the virus.

[IDIOTA]

i am skeptical of overly broad approaches like inhibiting reverse transcription so that HIV cannot encode its genetic information. what other processes depend on reverse transcription and would they be dampened or halted as well in the presence of one of baltimore's drugs?